The objective of the proposed research is to determine the role of lipid-lipid and lipid-protein interactions in the regulation of cholesteryl ester levels during atherogenesis. The kinetic and thermodynamic parameters which govern the reaction, cholesteryl ester plus water yields (reversibly) cholesterol plus fatty acid, and the properties of the enzyme, aortic cholesterol esterase, which catalyzes it, will be determined. The equilibrium position and rate constants for the reaction will be determined as a function of pH, ionic strength, substrate packing density and substrate composition. The experimental system will be comprised of well defined monolayers of substrates at either an air-water or oil-water interface with cholesterol esterase in an aqueous phase. Such a system will allow the reaction parameters to be determined accurately and reproducibly. Comparison of the data with the physical properties of the lipids measured in monolayers will allow the identificaton and quantitation of lipid-lipid and lipid-enzyme interactions. The specificities and magnitudes of these interactions will provide a basis for understanding the relationship between the intrinsic physico-chemical properties of aortic lipids and the accumulation of cholesteryl esters in the aorta.